Leukoencephalopathy in HAART-treated HIV-1+ Patients

HAART 治疗的 HIV-1 患者的白质脑病

• 批准号: 6656763
• 负责人: PASQUALE FERRANTE
• 金额: $ 12.5万
• 依托单位: FONDAZIONE DON CARLO GNOCCHI ONLUS
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6656763
• 关键词: AIDS /HIV neuropathy; AIDS therapy; HIV infections; T lymphocyte; cellular immunity; cerebrospinal fluid; clinical research; cytokine; enzyme linked immunosorbent assay; gene expression; human subject; human therapy evaluation; laser capture microdissection; longitudinal human study; magnetic resonance imaging; microarray technology; neuroimaging; neuropsychological tests; patient oriented research; polymerase chain reaction; progressive multifocal leukoencephalopathy

DESCRIPTION (provided by applicant): The advent of highly active antiretroviral therapy (HAART) has dramatically decreased the death rate due to HIV-1 infection in AIDS patients. However, the efficacy of HAART on HIV-1 associated complication of the central nervous system has remained at a lower level. Most notably, the incidence of white matter disease such as Progressive Multifocal Leukoencephalopathy (PML) appears to be less affected. Some studies show that only half of the PML patients benefit from HAART and show improved survival. Alarmingly, with the advent of HAART, PML remains a fast progressing disease in some patients, whereas other groups of patients show signs of PML with a slower progression. In addition, several new cases of anew leukoencephalopathy with no sign of active JCV replication, named non-determined leukoencephalopathy (NDLE), have been clinically diagnosed among AIDS patients under HAART treatment. In this R21 pilot research proposal, we will perform comprehensive longitudinal clinical, virological, and immunological studies on several AIDS patients under HAART exhibiting leukoencephalopathy to determine if a new variant of JCV is associated with slower progressing PML and if the new leukoencephalopathy is the result of imbalanced expression of cytokines and immunomodulators. The use of DNA microarray technology will provide us with compelling information on the profile of cellular gene expression in immune cells of AIDS patients with fast and slow progressing PML, as well as those exhibiting NDLE.

描述（由申请人提供）：高效抗逆转录病毒疗法（HAART）的出现极大地降低了艾滋病患者因感染HIV-1而导致的死亡率。然而，HAART对HIV-1相关中枢神经系统并发症的疗效仍处于较低水平。最值得注意的是，白质疾病（例如进行性多灶性白质脑病（PML））的发病率似乎受到的影响较小。一些研究表明，只有一半的 PML 患者从 HAART 中受益并显示出生存率的提高。令人担忧的是，随着 HAART 的出现，PML 在某些患者中仍然是一种快速进展的疾病，而其他患者群体则显示出进展较慢的 PML 迹象。此外，在接受HAART治疗的艾滋病患者中，临床诊断出几例新的无活跃JCV复制迹象的新白质脑病病例，称为未确定白质脑病（NDLE）。在这个 R21 试点研究计划中，我们将对几名接受 HAART 治疗并表现出白质脑病的 AIDS 患者进行全面的纵向临床、病毒学和免疫学研究，以确定 JCV 的新变种是否与进展缓慢的 PML 相关，以及新的白质脑病是否是由细胞因子和免疫调节剂的表达失衡。 DNA 微阵列技术的使用将为我们提供关于患有快速和缓慢进展的 PML 以及表现出 NDLE 的艾滋病患者免疫细胞中细胞基因表达谱的令人信服的信息。